Diabetes Pancreas o Exocrine function digestive enzymes o Endocrine function Hormones Insulin Glucagon o Help regulate energy reserves in the body Insulin o Insulin is a polypeptide hormone secreted by beta cells of endocrine pancreas islets of Langerhans o Insulin is stored in beta cells made from a precursor protein known as pro insulin Another hormone amylin is released with insulin o Insulin is stored in secretory granules A cell releases insulin when stimulated by glucose Glucose enters the cell and triggers a cascade of biochemical events that increase cytoplasmic concentration of calcium One of the events triggered by glucose is closure of potassium channels which leads to opening of calcium channels and influx of calcium Influx of calcium increases cytoplasmic calcium concentration which stimulates insulin release into the cell Effects of Insulin o Insulin is first released into portal circulation reaches liver where approximately gets degraded The rest gets into systemic circulation o In systemic circulation insulin circulates unbound to plasma proteins Half life in circulation is short 5 6 minutes o In peripheral tissues insulin binds to its own receptors on plasma membrane insulin receptors o Binding of insulin to its receptor triggers a series of biochemical events including insertion of glucose transporters into the cell surface membrane These effects are countered by other hormones including epinephrine glucagon growth hormone and cortisol Insulin Target Tissues o Liver Insulin stimulates storage of glucose as glycogen o Adipose tissue Insulin stimulates storage of glucose as triglycerides fat o Muscle Insulin stimulates storage of amino acids as proteins and glucose as glycogen Diabetes Mellitus o Diabetes is Greek for runs through and Mellitus means honey or sweet Refers to Polyuria o Diabetes mellitus is characterized by Hyperglycemia Altered metabolism of Carbohydrates Lipids Proteins Increased risk of vascular complications Classification of Diabetes Mellitus o Type I Insulin Dependent Diabetes Mellitus Early adulthood juvenile onset diabetes Autoimmune disease destruction of cells Exogenous insulin required for survival 10 of cases o Type II Non Insulin Dependent Diabetes Mellitus Some insulin function Maturity onset diabetes mellitus exceptions Obesity Decreased response of peripheral tissues to insulin insulin resistance 90 of cases Complications o Acute Complications Hyperglycemia 200 mg ml blood glucose Causes protein glycosylation HbA1c 8 Excessive urination thirst Fatigue nervousness poor wound healing Dry itchy skin Diabetic Ketoacidosis Body makes acetone and other ketones Can lead to acid blood Hyperosmolar Hyperglycemic State HHS o Chronic Complications Macrovascular complications Vascular disease including MI or stroke Microvascular complications Can lead to coma Body retains glucose increasing osmolarity of blood with or without ketosis Peripheral neuropathy leading to amputation due to infections gangrene or foot ulcers Blindness from cataracts glaucoma or retinopathy Renal failure Sexual dysfunction due to autonomic neuropathy Insulin Treatment o Insulin is a protien If it were taken orally it would be degraded in the gastrointestinal tract o Insulin is usually administered subcutaneously o It can be also administered intramuscularly o Only regular Insulin Indications o Type 1 Insulin dependent diabetes mellitus o Type 2 Non insulin dependent diabetes mellitus Insulin can be administered intravenously Severe infection After major surgery Severe trauma Pregnancy o Sometimes used to treat hyperkalemia high blood potassium levels Classification of Insulin Preparations By similarity to human insulin Porcine discontinued in 2006 Human a biosynthetic human insulin Modified Human Lispro Aspart Glargine mutations to change lifetime in body By duration of action Rapid acting o Regular Insulin prototype o Insulin Lispro Glulisine or Aspart Intermediate acting o NPH Insulin Neutral Protamine Hagendorn o Lispro or Aspart protamine Long acting o Glargine clear like regular insulin o Detemir Levemir approved 05 By Route of Administration Injected classic route includes jet injectors insulin pens and other types of dosers o Insulin pump a variation on injection o IV regular insulin o Inhaled Exubera released late 2006 but removed 2007 o Sublingual transdermal absorption Under clinical trials o Transplantation of pancreatic cells Experimental o Hypoglycemia Increased anxiety Confusion Blurred vision Cold sweating dizziness Headache Increased pulse Complications of Insulin Therapy rate o Lipodystrophies allergic reactions Significant Drug Interaction o Significant Drug Interactions Glucocorticosteroids e g Prednisone May increase blood glucose Alcohol May hypoglycemic effect of insulin blockers May mask symptoms of hypoglycemia may prolong hypoglycemia Oral antidiabetic agents Combination with insulin generally not advocated but is done for type 2 diabetics Insulin Dosing o Want to keep blood glucose in normal range 60 mg ml and 200 mg ml or less than 8 HbA1c Insulin Dosing Problems o Monitor blood sugar and glycosylated hemoglobin HbA1c o Dawn phenomenon and Somogyi effect require special attention Insulin Dosing and implications for AT and PT o Exercise has an insulin like effect on muscle causing uptake of glucose amino acids o Exercise after insulin may require a snack or decreased insulin dose to maintain blood glucose o One of the safest times for exercise is after a meal with short acting insulin prior to the meal o Target Heart Rates should be established after taking a stress test to establish max heart rate o No exercise should be done if fasting glucose levels are 280 mg dL reduce prior to exercise and monitor glucose prior during and after exercise o Increased body temperature increases the rate of absorption of SC insulin Oral Hypoglycemic Agents o Sulfonylureas o Mechanism of Action Stimulation of release of insulin from cells Increase the sensitivity of peripheral tissues to insulin o The predominant effect of traditional oral hypoglycemic agents is on insulin secretion o These agents are not effective in patients who have no endogenous insulin Type 1 diabetes o Traditional oral hypoglycemic agents sulfonylureas close potassium channels on pancreatic cells which opens o calcium channels influx of calcium stimulates insulin release Sulfonylueras o Indication Uncomplicated non insulin dependent diabetes mellitus Type 2 in persons whose diabetes